Cytokines and chemokines involved in acute retinal necrosis

PURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus– associated Fuchs’ uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. RESULTS. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and leve

Dutch juvenile idiopathic arthritis patients, carers and clinicians create a research agenda together following the James Lind Alliance method: A study protocol

Background: Research on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research. Main body: Dutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a 'Priority Setting Partnership' (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way. Conclusion: A JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters

Ocular complications in children within 1 year after hematopoietic stem cell transplantation

Importance: It is essential to have insights into the risk of ocular involvement after hematopoietic stem cell transplantation (HSCT) in the pediatric population because young and severely ill children are unaware of their ocular problems. Objective: To study the development of ocular complications in children within 1 year after HSCT. Design and Setting: This prospective study includes all consecutive patients who had undergone an HSCT at the Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands, in 2009 and 2010. Participants: Forty-nine consecutive patients underwent systematic ophthalmologic evaluations before HSCT, before leaving the HSCT unit after HSCT, and 3, 6, and 12 months after HSCT. Additional examinations were performed during systemic viral reactivations. Main Outcome Measure: Development of ocular complications, including uveitis, hemorrhagic complications, optic disc edema, and dry eye syndrome. Results: Thirteen patients (27%) developed an ocular complication after HSCT. These complications included DES (n=7 [14%]), (sub)retinal hemorrhage (n=6 [12%]), optic disc edema (n=3 [6%]), chorioretinal lesions (n=2 [4%]), vitritis (n=1 [2%]), and increased intraocular pressure (n=1 [2%]). Median time to the development of dry eye syndrome was 5 months after HSCT, whereas all other ocular complications were detected within the first 3months after HSCT. In most cases, the symptoms were mild and self-limiting. Children with malignant disease had a higher risk of the development of ocular complications compared with children with nonmalignant disease. Conclusions and Relevance: Ocular complications in pediatric HSCT patients are common, although mostly mild. The risk of viral uveitis development during systemic viral reactivations is low; however, the potential risk of vision-threatening complications in this population cannot be ruled out. Copyrigh

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy

__Background__ Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. __Methods__ 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with noninfectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. __Results__ The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLAA* 2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA ( p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. __Conclusions__ We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition